Synthesis of racemic (+) and (-) N-[methyl-11C]nomifensine, a ligand for evaluation of monoamine re-uptake sites by use of positron emission tomography

The synthesis of racemic or enantiomeric N-[methyl-11C]nomifensine (1,2,3,4-tetrahydro-2-[11C]methyl-4-phenyl-8-isoquinolinamine), a potential ligand for the evaluation of monoamine re-uptake sites at the presynaptic dopaminergic terminals, using the appropriate N-desmethylcompounds and [11C]methyl iodide is described. The radiochemical conversion of [11C]methyl iodide to [11C]nomifensine was in the order of 85-95%. Radiochemical purity of the LC-purified radiopharmaceutical was in the order of 98-99%. In a typical run, starting with 120 mCi (4.4 GBq) of [11C]carbon dioxide, 380 MBq of a final solution was obtained within 55 min (roughly 20 min of that is related to transport time). The specific radioactivity corresponding to the [11C]methyl iodide was 30-100 mCi/μmol (typical: a total mass of 30 μg and 150 MBq was administered in the PET-studies). A procedure for resolving the racemate of N-desmethylnomifensine (1,2,3,4-tetrahydro-4-phenyl-8-isoquinoline) into its enantiomers using triacetylcellulose as the stationary phase and methanol/ethanol as solvents by use of LC is also described. (author)